Non-contrast-enhanced breast MRI for evaluation of tumor volume change after neoadjuvant chemotherapy.

PURPOSE: Three-dimensional contrast-enhanced magnetic resonance imaging (3D-Ce-MRI) is a most powerful tool for evaluation of neoadjuvant chemotherapy (NAC). However, the use of contrast agent is invasive, expensive, and time consuming, Thus, contrast agent-free imaging is preferable. We aimed to investigate the tumor volume change after NAC using maximum intensity projection diffusion-weighted image (MIP-DWI) and 3D-Ce-MRI. METHOD: We finally enrolled 55 breast cancer patients who underwent NAC in 2018. All MRI analyses were performed using SYNAPSE VINCENT® medical imaging system (Fujifilm Medical, Tokyo, Japan). We evaluated the tumor volumes before, during, and after NAC. Tumor volume before NAC on 3D-Ce-MRI was termed Pre-CE and those during and after NAC were termed Post-CE. The observer raised the lower end of the window width until the tumor was clearly visible and then manually deleted the non-tumor tissues. A month thereafter, the same observer who was blinded to the 3D-Ce-MRI results randomly evaluated the tumor volumes (Pre-DWI and Post-DWI) using MIP-DWI with the same method. Tumor volume change between ΔCE (Pre-CE - Post-CE/Pre-CE) and ΔDWI (Pre-DWI - Post-DWI/Pre-DWI) and the processing time for both methods (Time-DWI and Time-CE) were compared. RESULTS: We enrolled 55 patients. Spearman's rho between ΔDWI and ΔCE for pure mass lesions, and non-mass enhancement (NME) was 0.89 (p < 0.01), 0.63(p < 0.01) respectively. Time-DWI was significantly shorter than Time-CE (41.3 ± 21.2 and 199.5 ± 98.3 respectively, p < 0.01). CONCLUSIONS: Non-contrast-enhanced Breast MRI enables appropriate and faster evaluation of tumor volume change after NAC than 3D-Ce-MRI especially for mass lesions.

Preliminary study of standardized semiquantitative method for ultrasonographic breast composition assessment.

PURPOSE: To develop a classification tree via semiquantitative analysis for ultrasonographic breast composition assessment using routine breast ultrasonography examination images. METHODS: This study retrospectively enrolled 100 consecutive normal women who underwent screening mammography and supplemental ultrasonography. Based on sonographic breast composition, the patients' breasts were classified as nondense or dense, which were correlated with mammographic breast composition. Ultrasonographic breast composition was classified based on the fibroglandular tissue (FGT) thickness-to-subcutaneous fat and retromammary fat (FAT) thickness ratio. In addition, the presence of a high glandular tissue component (GTC) in FGT or the presence of evident fat lobules in FGT was investigated. The cutoff point between the nondense and dense breasts was calculated from the area under the curve (AUC). RESULTS: All cases with a high GTC were dense breasts, and all cases with evident fat lobules in the FGT were nondense breasts. The AUC of the FGT thickness-to-FAT ratio of all cases, the group without a high GTC, the group without evident fat lobules in the FGT, and the group without a high GTC or evident fat lobules in the FGT were 0.93, 0.94, 0.99, and 1, respectively. CONCLUSION: The presence of a high GTC indicated dense breasts, and the presence of evident fat lobules in the FGT represented nondense breasts. For the remaining cases, the cutoff point of the FGT thickness-to-FAT thickness ratio was 0.93 for ultrasonographic two-grade scale breast composition assessment with 100% accuracy.

Inter- and intra-observer variability of qualitative visual breast-composition assessment in mammography among Japanese physicians: a first multi-institutional observer performance study in Japan.

BACKGROUND: Visual assessment of mammographic breast composition remains the most common worldwide, although subjective variability limits its reproducibility. This study aimed to investigate the inter- and intra-observer variability in qualitative visual assessment of mammographic breast composition through a multi-institutional observer performance study for the first time in Japan. METHODS: This study enrolled 10 Japanese physicians from five different institutions. They used the new Japanese breast-composition classification system 4th edition to subjectively evaluate the breast composition in 200 pairs of right and left normal mediolateral oblique mammograms (number determined using precise sample size calculations) twice, with a 1-month interval (median patient age: 59 years [range 40-69 years]). The primary endpoint of this study was the inter-observer variability using kappa (κ) value. RESULTS: Inter-observer variability for the four and two classes of breast-composition assessment revealed moderate agreement (Fleiss' κ: first and second reading = 0.553 and 0.587, respectively) and substantial agreement (Fleiss' κ: first and second reading = 0.689 and 0.70, respectively). Intra-observer variability for the four and two classes of breast-composition assessment demonstrated substantial agreement (Cohen's κ, median = 0.758) and almost perfect agreement (Cohen's κ, median = 0.813). Assessments of consensus between the 10 physicians and the automated software Volpara® revealed slight agreement (Cohen's κ; first and second reading: 0.104 and 0.075, respectively). CONCLUSIONS: Qualitative visual assessment of mammographic breast composition using the new Japanese classification revealed excellent intra-observer reproducibility. However, persistent inter-observer variability, presenting a challenge in establishing it as the gold standard in Japan.

Investigation of imaging features in contrast-enhanced magnetic resonance imaging of benign and malignant breast lesions.

PURPOSE: This study aimed to enhance the diagnostic accuracy of contrast-enhanced breast magnetic resonance imaging (MRI) using gadobutrol for differentiating benign breast lesions from malignant ones. Moreover, this study sought to address the limitations of current imaging techniques and criteria based on the Breast Imaging Reporting and Data System (BI-RADS). MATERIALS AND METHODS: In a multicenter retrospective study conducted in Japan, 200 women were included, comprising 100 with benign lesions and 100 with malignant lesions, all classified under BI-RADS categories 3 and 4. The MRI protocol included 3D fast gradient echo T1- weighted images with fat suppression, with gadobutrol as the contrast agent. The analysis involved evaluating patient and lesion characteristics, including age, size, location, fibroglandular tissue, background parenchymal enhancement (BPE), signal intensity, and the findings of mass and non-mass enhancement. In this study, univariate and multivariate logistic regression analyses were performed, along with decision tree analysis, to identify significant predictors for the classification of lesions. RESULTS: Differences in lesion characteristics were identified, which may influence malignancy risk. The multivariate logistic regression model revealed age, lesion location, shape, and signal intensity as significant predictors of malignancy. Decision tree analysis identified additional diagnostic factors, including lesion margin and BPE level. The decision tree models demonstrated high diagnostic accuracy, with the logistic regression model showing an area under the curve of 0.925 for masses and 0.829 for non-mass enhancements. CONCLUSION: This study underscores the importance of integrating patient age, lesion location, and BPE level into the BI-RADS criteria to improve the differentiation between benign and malignant breast lesions. This approach could minimize unnecessary biopsies and enhance clinical decision-making in breast cancer diagnostics, highlighting the effectiveness of gadobutrol in breast MRI evaluations.

Rethinking screening mammography in Japan: next-generation breast cancer screening through breast awareness and supplemental ultrasonography.

Breast cancer mortality has not been reduced in Japan despite more than 20 years of population-based screening mammography. Screening mammography might not be suitable for Japanese women who often have dense breasts, thus decreasing mammography sensitivity because of masking. The J-START study showed that breast ultrasonography increases the sensitivity and the detection rate for early invasive cancers and lowers the rate of interval cancers for Japanese women in their 40 s. Breast awareness and breast cancer survival are directly correlated; however, breast awareness is not widely known in Japan. Next-generation breast cancer screening in Japan should consist of breast awareness campaigns for improving breast cancer literacy and supplemental breast ultrasonography to address the problem of false-negative mammograms attributable to dense breasts.

Overcoming the limitations of screening mammography in Japan and Korea: a paradigm shift to personalized breast cancer screening based on ultrasonography.

Screening mammography programs have been implemented in numerous Western countries with the aim of reducing breast cancer mortality. However, despite over 20 years of population-based screening mammography, the mortality rates in Japan and Korea continue to rise. This may be due to the fact that screening mammography is not as effective for Japanese and Korean women, who often have dense breasts. This density decreases the sensitivity of mammography due to a masking effect. Therefore, the early detection of small invasive cancers requires more than just mammography, particularly for women in their 40s. This review discusses the limitations and challenges of screening mammography, as well as the keys to successful population-based breast cancer screening in Japan and Korea. This includes a focus on breast ultrasonography techniques, which are based on histopathologic anatomical knowledge, and personalized screening strategies that are based on risk assessments measured by glandular tissue components.

Non-mass lesions on breast ultrasound: why does not the ACR BI-RADS breast ultrasound lexicon add the terminology?

The definition of a non-mass lesion on breast ultrasound (US) is designed for everyday practice to provide unambiguous clinical management and to assist physicians and sonographers as they interpret breast US images. The field of breast imaging research requires consistent and standardized terminology for non-mass lesions identified on breast US, especially when differentiating benign from malignant lesions. Physicians and sonographers should be aware of the benefits and limitations of the terminology and use them precisely. I am hopeful that the next edition of the Breast Imaging Reporting and Data System (BI-RADS) lexicon will include standardized terminology for describing non-mass lesions detected on breast US.

Artificial intelligence computer-aided detection enhances synthesized mammograms: comparison with original digital mammograms alone and in combination with tomosynthesis images in an experimental setting.

BACKGROUND: It remains unclear whether original full-field digital mammograms (DMs) can be replaced with synthesized mammograms in both screening and diagnostic settings. To compare reader performance of artificial intelligence computer-aided detection synthesized mammograms (AI CAD SMs) with that of DM alone or in combination with digital breast tomosynthesis (DBT) images in an experimental setting. METHODS: We compared the performance of multireader (n = 4) and reading multicase (n = 388), in 84 cancers, 83 biopsy-proven benign lesions, and 221 normal or benign cases with negative results after 1-year follow-up. Each reading was independently interpreted with four reading modes: DM, AI CAD SM, DM + DBT, and AI CAD SM + DBT. The accuracy of probability of malignancy (POM) and five-category ratings were evaluated using areas under the receiver operating characteristic curve (AUC) in the random-reader analysis. RESULTS: The mean AUC values based on POM for DM, AI CAD SM, DM + DBT, and AI CAD SM + DBT were 0.871, 0.902, 0.895, and 0.909, respectively. The mean AUC of AI CAD SM was significantly higher (P = 0.002) than that of DM. For calcification lesions, the sensitivity of SM and DM did not differ significantly (P = 0.204). The mean AUC for AI CAD SM + DBT was higher than that of DM + DBT (P = 0.082). ROC curves based on the five-category ratings showed similar proximity of the overall performance levels. CONCLUSIONS: AI CAD SM alone was superior to DM alone. Also, AI CAD SM + DBT was superior to DM + DBT but not statistically significant.

Comparisons between artificial intelligence computer-aided detection synthesized mammograms and digital mammograms when used alone and in combination with tomosynthesis images in a virtual screening setting.

PURPOSE: To compare the reader performance of artificial intelligence computer-aided detection synthesized mammograms (AI CAD SM) with that of digital mammograms (DM) when used alone or in combination with digital breast tomosynthesis (DBT) images. MATERIALS AND METHODS: This retrospective multireader (n = 4) study compared the reader performances in 388 cases (84 cancer, 83 benign, and 221 normal or benign cases). The overall accuracy of the breast-based assessment was determined by four radiologists using two sequential reading modes: DM followed by DM + DBT; and AI CAD SM followed by AI CAD SM + DBT. Each breast was rated by each reader using five-category ratings, where 3 or higher was considered positive. The area under the receiver-operating characteristic curve (AUC) and reading time were evaluated. RESULTS: The mean AUC values for DM, AI CAD SM, DM + DBT, and AI CAD SM + DBT were 0.863, 0.895, 0.886, and 0.902, respectively. The mean AUC of AI CAD SM was significantly higher (P < 0.0001) than that of DM. The mean AUC of AI CAD SM + DBT was higher than that of DM + DBT (P = 0.094). A significant reduction in the reading time was observed after using AI CAD SM + DBT when compared with that after using DM + DBT (P < 0.001). CONCLUSION: AI CAD SM + DBT might prove more effective than DM + DBT in a screening setting because of its lower radiation dose, noninferiority, and shorter reading time compared to DM + DBT.

Sensitivity and specificity of screening mammography without clinical breast examination among Japanese women aged 40-49 years: analysis of data from the J-START results.

BACKGROUND: Current breast cancer screening programs worldwide offer only mammography for asymptomatic women, without clinical breast examination (CBE). The sensitivity and specificity of true asymptomatic screening mammography are important, especially in Japan. METHODS: This study used data from the Japan Strategic Anti-cancer Randomized Trial (J-START) results, and then calculated the sensitivity and specificity of screening mammography without CBE among Japanese women aged 40-49 years. RESULTS: The sensitivity and specificity of modern film mammography, performed biennially, among Japanese women aged 40-49 years were 71.7% and 92.6%, respectively. The sensitivity of mammography alone was 47.4%. From the secondary analysis, the sensitivity of mammography alone was 44.1% for women with dense breasts and 34.8% for women with non-dense breasts. CONCLUSION: The sensitivity of mammography alone of 47.4% is too low. The low sensitivity of screening mammography for true asymptomatic Japanese women aged 40-49 years places this population at an elevated risk, which can justify performing adjunctive ultrasonography.

Can breast MRI and adjunctive Doppler ultrasound improve the accuracy of predicting pathological complete response after neoadjuvant chemotherapy?

BACKGROUND: To examine the accuracy of MRI and Doppler ultrasound (US) for detecting residual tumor after neoadjuvant chemotherapy (NAC) for breast cancer and evaluate whether adjunctive Doppler US improves the MRI accuracy. METHODS: We reviewed 276 invasive breast cancer cases treated with NAC. Tumors were classified into four subtypes based on estrogen receptor and HER2 status. Response to NAC was evaluated using contrast-enhanced MRI and Doppler US. Residual Doppler flow was assumed to indicate a residual tumor. MRI and Doppler findings were compared with the histopathological findings of resected specimens. Pathological complete response (pCR) was defined as neither in situ nor invasive cancer left. RESULTS: Of the 276 tumors, imaging complete responses were observed using MRI and Doppler US in 62 (22%) and 111 (40%), respectively, whereas pCR was achieved in 44 (16%). MRI and Doppler US predicted residual tumor with 88% and 69% sensitivity, 80% and 91% specificity, 87% and 73% accuracy, 96% and 98% PPV, and 56% and 36% NPV, respectively. The accuracies of MRI and Doppler US were significantly higher for HER2-negative than HER2-positive tumors (p < 0.001 and p = 0.043, respectively). Seven (26%) of 27 false-negative cases identified by MRI were correctly diagnosed as positives with adjunctive Doppler US. CONCLUSIONS: Although MRI accurately detected residual tumor with 87% accuracy, this was still not sufficient to meet clinical demands and differed with tumor subtype. Adjunctive Doppler US in cases that appear to show a complete response on MRI might reduce chances of false negatives and increase the NPV of MRI for predicting residual tumor.

Evaluation of Breast Edema Findings at T2-weighted Breast MRI Is Useful for Diagnosing Occult Inflammatory Breast Cancer and Can Predict Prognosis after Neoadjuvant Chemotherapy.

Background Prediction of occult inflammatory breast cancer (IBC) and breast cancer prognosis based on breast edema findings on T2-weighted MRI scans, even for patients without clinical signs of IBC, would be useful in both pretreatment planning and prognosis and may elucidate the underlying biologic mechanisms. Purpose To evaluate whether classification of breast edema on T2-weighted MRI scans is useful for predicting the prognosis of patients with breast cancer treated with neoadjuvant chemotherapy (NAC). Materials and Methods A retrospective evaluation was performed of women with breast cancer who underwent breast MRI and were treated with NAC between January 2011 and December 2018. Breast edema on T2-weighted images was scored on a scale of 1 to 4, as follows: (a) breast edema score (BES) 1, no edema; (b) BES 2, peritumoral edema; (c) BES 3, prepectoral edema; and (d) BES 4, subcutaneous edema (suspicious for occult IBC). Clinically evident IBC was classified as BES 5 (without MRI). The log-rank test was performed, and hazard ratios were calculated using the Cox hazard model to evaluate associations between BES and progression-free survival (PFS) and overall survival (OS). PFS rate at 100 months after initiation of therapy was also evaluated. Results Of 408 patients (median age, 53 years; range, 28-80 years), 65 (16%) had a recurrence and 27 (7%) died. The log-rank test revealed differences in PFS for BES 4 versus 1, BES 5 versus 1, BES 5 versus 2, and BES 5 versus 3 (adjusted P < .05 for all). PFS rates for BES 1-5 were 0.92, 0.85, 0.80, 0.62, and 0.58, respectively, and the corresponding OS rates at 100 months were 0.98, 0.91, 0.92, 0.77, 0.86, respectively. Conclusion Classification of breast edema findings on T2-weighted MRI scans using a breast edema score was related to the prognosis of patients after neoadjuvant chemotherapy. © RSNA, 2021 Online supplemental material is available for this article.

Overall assessment system of combined mammography and ultrasound for breast cancer screening in Japan.

Mammography is the only screening method with evidence in support of reduced breast cancer mortality, but yields poor accuracy outcomes in women with dense breast tissue. The Japan Strategic Anti-cancer Randomized Trial (J-START) was conducted as part of the measures implemented to deal with women with dense breast tissue. Although the sensitivity was increased, the specificity was significantly lower in the intervention group because further examination was required in all positive cases classified by either mammography or ultrasound in the J-START. To address the issue, an overall assessment system of combined mammography and adjunctive ultrasound for breast cancer screening has been developed in Japan. The basic concept is based on a comprehensive assessment that includes a mammography assessment followed by an adjunctive assessment for ultrasound similar to the clinical setting. Currently, mammography alone is recommended for population-based breast cancer screening in Japan, but additional ultrasonography is extensively available for women, especially for women with dense breasts with shared decision-making for personalized breast cancer screening. The overall assessment system is recommended for use in Japan when breast cancer screening is conducted using both mammography and ultrasonography. In this article, we summarize the advantages of the overall assessment and the simultaneous mammography/ultrasound method, the basic approach used in Japan to assign the overall assessment category for breast cancer screening, and we outline the future directions of adjunctive screening ultrasound.

A deep learning-based automated diagnostic system for classifying mammographic lesions.

BACKGROUND: Screening mammography has led to reduced breast cancer-specific mortality and is recommended worldwide. However, the resultant doctors' workload of reading mammographic scans needs to be addressed. Although computer-aided detection (CAD) systems have been developed to support readers, the findings are conflicting regarding whether traditional CAD systems improve reading performance. Rapid progress in the artificial intelligence (AI) field has led to the advent of newer CAD systems using deep learning-based algorithms which have the potential to reach human performance levels. Those systems, however, have been developed using mammography images mainly from women in western countries. Because Asian women characteristically have higher-density breasts, it is uncertain whether those AI systems can apply to Japanese women. In this study, we will construct a deep learning-based CAD system trained using mammography images from a large number of Japanese women with high quality reading. METHODS: We will collect digital mammography images taken for screening or diagnostic purposes at multiple institutions in Japan. A total of 15,000 images, consisting of 5000 images with breast cancer and 10,000 images with benign lesions, will be collected. At least 1000 images of normal breasts will also be collected for use as reference data. With these data, we will construct a deep learning-based AI system to detect breast cancer on mammograms. The primary endpoint will be the sensitivity and specificity of the AI system with the test image set. DISCUSSION: When the ability of AI reading is shown to be on a par with that of human reading, images of normal breasts or benign lesions that do not have to be read by a human can be selected by AI beforehand. Our AI might work well in Asian women who have similar breast density, size, and shape to those of Japanese women. TRIAL REGISTRATION: UMIN, trial number UMIN000039009. Registered 26 December 2019, https://www.umin.ac.jp/ctr/.

Is the presence of edema and necrosis on T2WI pretreatment breast MRI the key to predict pCR of triple negative breast cancer?

PURPOSE: Given that a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is an important prognostic factor, evaluating pretreatment imaging findings is important. Outcomes for triple negative breast cancer (TNBC) vary with the histological classification, indicating that this classification is clinically significant. In this study, we focus on the most common histological subtype of TNBC, invasive carcinoma of no special type (NST), to evaluate whether intramammary edema (intra-E) and intratumoral necrosis (intra-N) on T2-weighted magnetic resonance imaging (T2WI) is a useful predictor of pCR. METHOD: We retrospectively included patients with biopsy-diagnosed TNBC-NST who received NAC between January 2014 and December 2017. Intra-E and intra-N were evaluated on T2WI before NAC. We grouped intra-E into no edema, peritumoral edema, prepectoral edema, and subcutaneous edema, and we defined intra-N as water-like signal intensity without enhancement on T2WI. We also evaluated tumor size, Ki-67 expression, and histological/nuclear grade, as well as their correlation with intra-E and intra-N. RESULTS: Fifty-seven patients with TNBC-NST were enrolled. There was no correlation with the rate of pCR and the presence of either intra-E or intra-N before NAC. Only intra-E and tumor size showed a positive correlation. CONCLUSIONS: In patients with TNBC-NST, intra-E and intra-N did not correlate with pCR, but intra-E did positively correlate with tumor size. NST may exhibit a greater response to NAC, regardless of whether intra-E or intra-N is present or not on the pretreatment MRI. KEY POINTS: • Pathological complete response in TNBC-NST had no correlation with intramammary edema or intratumoral necrosis. • NAC may be justified in TNBC-NST even in the presence of edema or necrosis. • The extension of edema correlated with tumor size of TNBC-NST.

The Japanese Breast Cancer Society Clinical Practice Guidelines, 2018 edition: the tool for shared decision making between doctor and patient.

The Breast Cancer Clinical Practice Guidelines, 2018 edition, written in Japanese and organized by the Japanese Breast Cancer Society, were published in Japanese in May 2018. The process of making these guidelines, as well as the content, was largely changed and compared with previous editions. The concept of these guidelines is to act as a support tool for shared decision making between doctor and patient. The procedure of creating the guidelines referred to Minds Handbook for Clinical Practice Guideline Development 2014. This guideline, written in Japanese, consists of two booklets: (1) the epidemiology and diagnosis booklet covering screening, radiological, and pathological diagnosis and (2) the treatment booklet covering surgical therapy, radiation therapy, and systemic therapy. This review article consists of five parts, including the history of the Breast Cancer Clinical Practice Guidelines, the concept, process, content, and recommendation grade. I believe this brief summary concerning the Breast Cancer Clinical Practice Guidelines 2018 edition in English will be helpful for both Japanese and foreign investigators.